Significance of the serum level of soluble E-cadherin in patients with HCC

BACKGROUND/AIMS: E-cadherin (E-cad) is a type of adhesion molecule, and recent studies have demonstrated a correlation between its expression in tumor lesions and the recurrence of HCC. Serum levels of soluble E-cad are significantly elevated in patients with several types of cancer. The authors evaluated the significance of the serum level of soluble E-cad as a predictor of early recurrences (intrahepatic or extrahepatic metastasis) of HCC after a curative resection. METHODOLOGY: The concentrations of soluble E-cad in the serum of 25 HCC patients before surgery and 12 healthy subjects were measured using a sandwich enzyme-linked immunosorbent assay. The hepatic expression of E-cad was examined by immunohistochemical staining. RESULTS: The median serum soluble E-cad levels were significantly elevated in HCC patients before surgery in comparison to those in healthy subjects (10,759 ng/mL vs. 5,798 ng/mL, p < 0.05). The patients in the high serum soluble E-cad group experienced a higher incidence of early recurrence (p < 0.05). The levels of expression of E-cad in HCC lesions were not related to the serum levels of soluble E-cadherin. CONCLUSIONS: The study demonstrated that serum soluble E-cad levels were elevated in patients with HCC, and high serum soluble E-cadherin (> or = 8,000 ng/ml) was associated with early recurrence or extrahepatic metastasis. Serum soluble E-cad may therefore be a potential prognostic marker for HCC.     

Endoscopic radial artery harvesting: patient satisfaction and complications

Endoscopic radial artery harvesting was recently introduced to reduce the morbidity associated with conventional open harvesting and improve cosmetic outcomes. From January 2004 through December 2006, 25 radial arteries were harvested endoscopically from 25 patients using the VasoView endoscopic system. Bilateral radial arteries were harvested from 6 patients by both the endoscopic and open techniques, and postoperative patient satisfaction was assessed using a visual analogue scale. Mean harvesting time was 61.9 +/- 16.0 min (range, 44-105 min), and mean harvested conduit length was 16.8 +/- 2.0 cm (range, 15-19 cm). Objective dorsal thenar numbness remained in 2 patients (8%); none complained of forearm numbness. All patients expressed marked satisfaction with the endoscopic technique and the small incision. Patient satisfaction was significantly higher with the endoscopic technique than with the open technique (visual analogue scale of 9 vs 5). Postoperative angiography revealed occlusion of a graft that had been anastomosed to a small diagonal branch. The overall graft patency was 96.6%. Endoscopic radial artery harvesting can be performed safely with infrequent complications. This method results in excellent patient satisfaction, particularly regarding the cosmetic outcome.     

Severe cerebral calcification in a case of LEOPARD syndrome

We report severe brain calcification in a case of LEOPARD syndrome that has not been reported in the literature. A 53-year-old Japanese man presented with generalized lentigines, arrhythmia, gonadal hypoplasia, endocrine abnormality, mental retardation and skeletal abnormalities, and was consequently diagnosed as LEOPARD syndrome. Brain computed tomography demonstrated surprisingly dense and symmetric calcifications in the cerebellar dentate nuclei, cerebral basal ganglia, thalamus, and cerebral white matter. It may be an incidental idiopathic calcification. Alternatively it may be a rare clinical manifestation of LEOPARD syndrome.     

Endothelial progenitor cells: therapeutic target for cardiovascular diseases

Circulating endothelial progenitor cells (EPCs) derived from bone marrow were isolated for the first time in 1997 and characterized. Recent evidence has indicated that EPCs contribute to re-endothelialization of injured vessels as well as neovascularization of ischemic lesions and that a decrease in the number of EPCs is an independent predictor of morbidity and mortality of cardiovascular diseases. These finding suggest that EPCs play a major role in the pathogenesis of atherosclerosis and cardiovascular diseases. Interestingly, the number and function of EPCs are regulated by not only various kinds of angiogenic cytokines and cardiovascular risk factors per se but also some interventions, including lifestyle modification (aerobic exercise, body weight loss, and smoking cessation) and pharmacological therapy (e.g., renin-angiotensin system inhibitor, statin, and erythropoietin). It is thought that regulation of the number and function of EPCs directly influences the maintenance and development of atherosclerosis. Therefore, it is clinically important to estimate the degree of EPC bioactivity and to increase the EPC bioactivity by appropriate interventions. In this review, we focus on the relationship between EPCs and cardiovascular risk factors and the role of EPCs in cardiovascular diseases.     

Remarkable shrinkage of sarcomatoid renal cell carcinoma with single-agent gemcitabine

A 60-year-old Japanese man presented to our hospital with a painful left hip. Computed tomography showed a tumor in the left kidney and metastases in the left gluteus maximus muscle and lung. The pathological diagnosis of a biopsy specimen obtained from a metastatic lesion in the left gluteus maximus muscle was sarcomatoid renal cell carcinoma. On admission, his general condition was extremely poor. He was confined to bed because of severe left hip pain and confusion, possibly caused by hypercalcemia. This seriously ill patient suffering from advanced sarcomatoid renal cell carcinoma was treated with single-agent gemcitabine, resulting in symptom relief and a dramatic improvement in his status; all of the tumors had regressed significantly by the 11th dose of gemcitabine. These findings indicate that single-agent gemcitabine is one of the few chemotherapeutic agents effective for palliation in patients with sarcomatoid renal cell carcinoma, even those with poor performance status.     

Preventive effect of N-acetylcysteine on contrast-induced nephropathy following coronary angiography and angioplasty

Contrast-induced nephropathy (CIN) is one of the serious side effects of contrast media. A few studies have suggested that N-acetylcysteine (NAC) is effective to prevent CIN, but the efficacy remains unclear in Japanese. Therefore, we retrospectively studied the preventive effect of NAC on CIN in Sakakibara Heart Institute. Patients who had been administered NAC for the purpose of preventing CIN before coronary intervention between February 2005 and November 2006 were included in the NAC group. In addition, age- and rate of diabetes mellitus-matched controls were randomly extracted. We retrieved and analyzed patient data including demographics, NAC dosage, and serum creatinine concentrations (Scr). NAC group (n=16) showed significantly higher baseline Scr (p<0.01) and a tendency toward a lower dose of contrast media (p=0.068) compared with controls (n=48). Since the occurrence of CIN was low, there was no significant difference in the proportion of CIN between the groups (NAC: 6%, controls: 4%). NAC group trended toward a decrease in Scr after the use of contrast media, while controls increased (-0.04+/-0.25 versus +0.03+/-0.36 mg/dl, p=0.096). The multivariate analysis showed that the dosage of NAC is inversely correlated with Scr independent of baseline Scr and dosage of contrast media. Despite higher baseline Scr (i.e., high-risk with CIN) in the NAC group, the real Scr value reflected a lower trend on average. In addition, this finding suggests that a larger dose of NAC results in a lower Scr value, we consider that the NAC dosage more likely prevented CIN.     

Induction of characteristic hepatocyte proliferative lesion with dietary exposure of Wistar Hannover rats to tocotrienol for 1 year

Tocotrienol is an antioxidant which has found commercial application as a food additive and health supplement all over the world. Since there have been no reports regarding toxicological effects of long-term exposure, we performed a 52-week chronic study using Wistar Hannover rats of both sexes given the compound at doses of 0, 0.08, 0.4 or 2% in powdered basal diet. Since 6 animals in the 2% male group died of hemorrhage of several organs by week 50, the maximum dose level was changed to 1% in both sexes for the last 2 weeks. Decrease of body weight gain was observed in the 2% males from week 5 and females from week 10, this persisting to the end of the study. With the high dose, prolongation of prothrombin time and increase of serum ALT in males, and increase of serum ALP in both sexes were observed with statistical significance. In male and female rats receiving 0.4% or less, there were no toxicological changes in any of the parameters examined. At necropsy, multiple cyst-like nodules on the liver surface were macroscopically pronounced in both sexes receiving 2%. On histopathological examination, hepatocellular nodules were evident with distortion of hepatic cords and compression of the surrounding tissue, almost all including areas of spongiosis hepatis. The constituent hepatocytes were immunohistochemically stained with proliferation cell nuclear antigen at high rates. Nevertheless, they did not exhibit overt atypia and the basic lobular architecture remained intact. Additionally, they were consistently negative for glutathione S-transferase placental form (GST-P). Accordingly, we propose the newly categorized but previously used name 'nodular hepatocellular hyperplasia', which may not necessarily have a neoplastic or regenerative nature. However, quantitative GST-P analysis of the liver sections overall showed numbers of GST-P foci in the high dose females to be significantly elevated as compared to the control value. Based on the present data demonstrating nodular liver lesions only at the high dose of both sexes, we conclude that the no-observed-adverse-effect level (NOAEL) is 0.4% (303mg/kg/day for males, and 472mg/kg/day for females).     

Phase IIa clinical study of [<Superscript>18</Superscript>F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors

Objective

[¹⁸F]Fluciclovine (anti-[¹⁸F]FACBC) has demonstrated diagnostic efficacy for cancers of the brain where [¹⁸F]fludeoxyglucose has limitations. We conducted a phase IIa study of anti-[¹⁸F]FACBC to assess its accumulation pattern and safety in patients with malignant glioma.

Methods

Five patients with glioma scheduled for brain tumor resection received anti-[¹⁸F]FACBC. Brain positron emission tomography (PET) was performed following intravenous administration of anti-[¹⁸F]FACBC, and subsequently, preoperative gadolinium contrast-enhanced T1-weighted (CE-T1W) magnetic resonance imaging (MRI) was performed for surgery. Specimens for histopathological evaluation were collected during surgery, and their location was precisely determined on CE-T1W MRI and anti-[¹⁸F]FACBC PET/CT images. In addition, tumor extent defined on the MRI and PET/CT images was compared. To determine time–activity curves for anti-[¹⁸F]FACBC uptake in brain tumor and normal tissues, regions of interest were set in the brain tumor, contralateral normal tissue and the cerebellum, and their standardized uptake values (SUV) were calculated. The safety of anti-[¹⁸F]FACBC was assessed based on subjective symptoms and objective findings, electrocardiograms, vital signs, laboratory results, and the incidence of adverse events.

Results

Anti-[¹⁸F]FACBC accumulated in the malignant gliomas of all patients. CE-T1W MRI detected gliomas in all patients, but anti-[¹⁸F]FACBC PET/CT generally delineated wider regions of tumor extent than CE-T1W MRI. Two of the histopathologically confirmed tumors were located in regions that were defined using anti-[¹⁸F]FACBC PET/CT, but not using CE-T1W MRI. Two patients experienced three mild adverse events: one complained of a dull headache and later a mild headache, and the other showed general malaise. These symptoms resolved spontaneously without treatment. Only the mild headache could not be ruled out from having a causal relationship with anti-[¹⁸F]FACBC. Favorable T/N ratios regarding anti-[¹⁸F]FACBC uptake between tumors and normal control tissues were demonstrated in this trial.

Conclusions

It is suggested that anti-[¹⁸F]FACBC PET/CT has the ability to delineate glioma spread that is undetectable using CE-T1W MRI. Anti-[¹⁸F]FACBC is safe in patients with malignant glioma.This study was registered in the Japan Pharmaceutical Information Center Clinical Trials Information, which is one of the World Health Organization registries (registration number: JapicCTI-111387).

     

Effect of Range and Angular Velocity of Passive Movement on Somatosensory Evoked Magnetic Fields

To clarify characteristics of each human somatosensory evoked field (SEF) component following passive movement (PM), PM1, PM2, and PM3, using high spatiotemporal resolution 306-channel magnetoencephalography and varying PM range and angular velocity. We recorded SEFs following PM under three conditions [normal range–normal velocity (NN), small range–normal velocity (SN), and small range–slow velocity (SS)] with changing movement range and angular velocity in 12 participants and calculated the amplitude, equivalent current dipole (ECD) location, and the ECD strength for each component. All components were observed in six participants, whereas only PM1 and PM3 in the other six. Clear response deflections at the ipsilateral hemisphere to PM side were observed in seven participants. PM1 amplitude was larger under NN and SN conditions, and mean ECD location for PM1 was at primary motor area. PM3 amplitude was larger under SN condition and mean ECD location for PM3 under SS condition was at primary somatosensory area. PM1 amplitude was dependent on the angular velocity of PM, suggesting that PM1 reflects afferent input from muscle spindle, whereas PM3 amplitude was dependent on the duration. The ECD for PM3 was located in the primary somatosensory cortex, suggesting that PM3 reflects cutaneous input. We confirmed the hypothesis for locally distinct generators and characteristics of each SEF component.